-
1.
Magnetic Resonance Imaging Quantification of Fasted State Colonic Liquid Pockets in Healthy Humans.
Murray, K, Hoad, CL, Mudie, DM, Wright, J, Heissam, K, Abrehart, N, Pritchard, SE, Al Atwah, S, Gowland, PA, Garnett, MC, et al
Molecular pharmaceutics. 2017;(8):2629-2638
Abstract
The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or "pockets". Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment.
-
2.
Early experience with customized, meal-triggered gastric electrical stimulation in obese patients.
Miras, M, Serrano, M, Durán, C, Valiño, C, Canton, S
Obesity surgery. 2015;(1):174-9
-
-
Free full text
-
Abstract
BACKGROUND We report our initial gastric electrical stimulation experience using the abiliti® system for the treatment of obese patients followed for 1 year. METHOD Between March 2011 and June 2013, 27 obese patients (BMI 30 to 46 kg/m(2)) were enrolled in a prospective open label study and implanted with a gastric stimulator. The patients were provided with nutritional support, and sensor-based behavioral feedback. RESULTS At 12 months, percent excess weight loss (%EWL) obtained was 49.3 ± 19.2 % with no significant differences between gender or age sub-groups. The %EWL data were segmented into two groups according to BMI 30-40 kg/m(2) patients (obesity grade I and II) and BMI >40 kg/m(2), with the results of weight loss being significantly higher for the lower BMI group (59.1 ± 19.5 vs. 46.7 ± 13.4, respectively, p < 0.01). One subject requested to have his device explanted, and the minor postoperative adverse events were resolved without hospital admission. All patients experienced early satiety and reduced their intake. CONCLUSIONS After 12 months of follow-up, gastric electrical stimulation treatment appears to be a safe and effective option for weight loss in obese subjects. Long-term follow-up and further studies are warranted.
-
3.
abiliti Closed-Loop Gastric Electrical Stimulation System for Treatment of Obesity: Clinical Results with a 27-Month Follow-Up.
Horbach, T, Thalheimer, A, Seyfried, F, Eschenbacher, F, Schuhmann, P, Meyer, G
Obesity surgery. 2015;(10):1779-87
-
-
Free full text
-
Abstract
BACKGROUND The aim of the study was to evaluate the safety and effectiveness of a novel closed-loop gastric electric stimulation device (abiliti system) featuring a transgastric sensor to detect food intake and an accelerometer to record physical activity to induce and maintain lifestyle changes to treat obesity. METHODS In a prospective, multi-center study, 34 obese subjects (BMI of 42.1 ± 5.3 kg/m(2)) who passed an eligibility evaluation were implanted with the abiliti system. Safety evaluation included an endoscopic exam to assess the intragastric electrode healing. Efficacy evaluation at 1 year of therapy included weight loss, improvements in eating, and exercise behavior and quality of life. RESULTS The transgastric implant controlled by endoscopy was stable for all participants. At 12 months (12 M) the mean excess weight loss (EWL) was 28.7% (95%CI, 34.5 to 22.5%), and mean reduction in BMI was 4.8 ± 3.2 kg/m(2). At 27 months (27 M), the EWL was 27.5% (95% CI, 21.3% to 33.7%). Eating behavior, evaluated by the "Three Factor Eating Questionnaire", showed a significant increase in the cognition factor and decrease in the disinhibition and hunger factors at 12 M in comparison to baseline (p < 0.001). Participants significantly increased their weekly physical activity (p < 0.001). Quality of life was improved in 55.2% of the patients. CONCLUSIONS Gastric electrical stimulation with abiliti system in obese participants is well tolerated and leads to significant 12 M weight loss, which was stable to 27 M. We suggest that weight loss is achieved due to the assessed alteration of eating behavior in particular the reduction in disinhibition and hunger, and the measured increase in physical activity.
-
4.
Effects of oral glucose intake on gastric myoelectrical activity and gastric emptying.
Misu, N, Kamiya, T, Kobayashi, Y, Hirako, M, Nagao, T, Shikano, M, Matsuhisa, E, Ando, T, Adachi, H, Kimura, G
Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi. 2004;(4-5):169-76
Abstract
To investigate the effect of oral glucose intake on gastric motility, we measured gastric myoelectrical activity and gastric emptying on two test conditions: 1) glucose intake and 2) water intake in the same 10 healthy male volunteers (20 to 29 years old). Gastric motility was evaluated with cutaneous-recorded electrogastrography (EGG) for 30 min both on fasting and after glucose or water intake, while gastric emptying was measured using acetaminophen-absorption method. There were no significant changes in EGG dominant frequency after water intake, but the frequency increased significantly after glucose intake. A postprandial dip (i.e., a transient decrease in frequency immediately after the food intake) was observed in 3 subjects after water intake and in 8 subjects following glucose intake. The EGG power ratio was significantly larger after glucose than water intake, with delayed gastric emptying in the former case. These results suggest that glucose is one of the components responsible for postprandial gastric motility.
-
5.
Gastric myoelectrical activity increases after moderate-intensity exercise with no meals under suppressed vagal nerve activity.
Kato, M, Sakai, T, Yabe, K, Miyamura, M, Soya, H
The Japanese journal of physiology. 2004;(3):221-8
-
-
Free full text
-
Abstract
Postprandial gastric myoelectrical activity recorded by electrogastrogram (EGG) with the subject in a supine position has shown to be enhanced after moderate-intensity pedaling exercise in an upright seated position, despite the suppression of vagal nerve activity. However, it is still unknown whether the effect is due to the exercise itself and/or a meal or how the position change has influenced the effects. To address this, we used a position-controllable cycle ergometer to examine the effects of the moderate-intensity exercise on EGG activity and the high-frequency (HF) component of heart rate variability (HRV), an index of vagal nerve activity. To eliminate the effect of position change, we carried out the exercise and the EGG recording in the supine position. The peak amplitude of the EGG was enhanced by prior moderate-intensity exercise with a reduced HF component of HRV, which did not differ for postexercise conditions with or without a meal. The small amount of meal itself, however, enhanced both the peak amplitude of the EGG and the HF component of HRV. The peak frequency of EGG was reduced and the instability coefficient of EGG was increased only after the exercise itself. Taken together, these results suggest that the enhanced amplitude of gastric myoelectrical activity can be induced by moderate-intensity exercise itself, even with suppressed vagal nerve activity, and that the mechanism underlying the exercise effects would differ from that underlying the effect of a meal alone.
-
6.
Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging.
Steingoetter, A, Kunz, P, Weishaupt, D, Mäder, K, Lengsfeld, H, Thumshirn, M, Boesiger, P, Fried, M, Schwizer, W
Alimentary pharmacology & therapeutics. 2003;(7):713-20
-
-
Free full text
-
Abstract
BACKGROUND Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric-retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research. AIM: To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric-retentive floating tablet using magnetic resonance imaging in the sitting position. METHODS A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food-filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5-T open-configuration magnetic resonance system. Volunteers were followed over a 4-h period. RESULTS Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance. CONCLUSION Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric-retentive tablets in the human stomach.
-
7.
Cholecystokinin and stomach distension combine to reduce food intake in humans.
Kissileff, HR, Carretta, JC, Geliebter, A, Pi-Sunyer, FX
American journal of physiology. Regulatory, integrative and comparative physiology. 2003;(5):R992-8
Abstract
The aim of this study was to test the hypothesis that gastric distension can enhance the effect of cholecystokinin (CCK) on reduction of food intake in men and women. Eight normal-weight subjects of each gender were tested four times each with either CCK or saline infusion crossed with gastric distension or no distension. Intravenous infusion of a low dose of CCK octapeptide (CCK-8; 112 ng/min for 23 min) combined with a subthreshold gastric distension induced by a water-filled balloon (300 ml) resulted in a significant (means +/- SED: 191 +/- 61 g in men, 209 +/- 61 g in women, and 200 +/- 43 g combined) reduction in intake of a liquid meal compared with saline infusion and unfilled gastric balloon. This combined effect was the result of a large and significant CCK effect when the stomach was distended (CCK vs. saline with distension: 169 +/- 43 g) and a small and insignificant distension effect (distension vs. no distension without CCK: 31 +/- 43 g). The CCK effect alone on intake (CCK vs. saline) without distension was not significant in men (72 +/- 61 g) but was significant in women (121 +/- 61 g). These results are consistent with the hypothesis that CCK's suppression of food intake is enhanced when the stomach is distended.
-
8.
Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?
Netzer, P, Gaia, C, Lourens, ST, Reber, P, Wildi, S, Noelpp, U, Ritter, EP, Ledermann, H, Lüscher, D, Varga, L, et al
Alimentary pharmacology & therapeutics. 2002;(1):119-27
-
-
Free full text
-
Abstract
BACKGROUND In previous studies, tropisetron has been shown to accelerate gastric emptying of a solid meal. However, it is uncertain whether other specific 5-hydroxytryptamine-3 receptor antagonists, such as ondansetron, also have a gastroprokinetic effect in humans. AIM: To evaluate the effect of ondansetron on gastric half-emptying time (T1/2) of a solid meal, gastric myoelectrical activity and hormone levels in 14 healthy volunteers. METHODS In a placebo-controlled, randomized, crossover study, we investigated the effects of ondansetron (8 mg intravenously) on the gastric emptying of solids (by scintigraphy), gastric myoelectrical activity (by electrogastrography) and the post-prandial release of cholecystokinin, gastrin, human pancreatic polypeptide, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, motilin, substance P and galanin. RESULTS The average T1/2 values were 86 min and 85.5 min without lag time (P=0.082) and 92 min and 93 min with lag time (P=0.158) for the placebo and ondansetron treatments, respectively. The average T1/2 of female volunteers was significantly longer than that of male volunteers. The dominant gastric electrical frequency and hormone plasma concentrations were not altered by ondansetron. CONCLUSIONS Ondansetron did not affect the gastric emptying of solids, the dominant gastric electrical frequency or the plasma concentrations of the analysed gastrointestinal peptides.
-
9.
Effects of nutrients and serotonin 5-HT3 antagonism on symptoms evoked by distal gastric distension in humans.
Ladabaum, U, Brown, MB, Pan, W, Owyang, C, Hasler, WL
American journal of physiology. Gastrointestinal and liver physiology. 2001;(2):G201-8
Abstract
Distal gastric distension may contribute to meal-related dyspeptic symptoms. This study's aims were to determine the effects of distinct nutrient classes on symptoms induced by distal gastric distension and their dependence on 5-hydroxytryptamine(3) (5-HT3) receptors. Nine healthy subjects rated pain, nausea, and bloating induced by isobaric distal gastric distensions (6-24 mmHg) during duodenal lipid, carbohydrate, protein, or saline perfusion after treatment with placebo or the 5-HT3 receptor antagonist granisetron (10 microg/kg iv). Distensions produced greater pain, nausea, and bloating with lipid at 1.5 kcal/min compared with saline (P < or = 0.02), primarily because of greater distal gastric volumes at each distending pressure. In contrast, carbohydrate and protein had no significant effect. At 3 kcal/min, lipid increased symptoms through a volume-independent as well as a volume-dependent effect. Granisetron did not affect symptom perception or gastric pressure-volume relationships. In conclusion, isobaric distal gastric distension produces more intense symptoms during duodenal lipid compared with saline perfusion. Symptom perception during distal gastric distension is unaffected by 5-HT3 receptor antagonism.
-
10.
An exaggerated sensory component of the gastrocolonic response in patients with irritable bowel syndrome.
Simrén, M, Abrahamsson, H, Björnsson, ES
Gut. 2001;(1):20-7
-
-
Free full text
-
Abstract
BACKGROUND/AIMS: Visceral hypersensitivity is a feature of the irritable bowel syndrome (IBS). Postprandial symptoms are common in these patients. The effects of nutrients on colonic perception in IBS are incompletely understood. SUBJECTS We studied 13 healthy subjects and 16 patients with IBS-eight had diarrhoea predominant (IBS-D) and eight constipation predominant (IBS-C) IBS. METHODS Colonic perception thresholds to balloon distension and viscerosomatic referral pattern were assessed before and after duodenal infusion of lipid or saline, respectively. At the end of the infusions, plasma levels of gastrointestinal peptides were determined. RESULTS Lipids lowered the thresholds for first sensation, gas, discomfort, and pain in the IBS group but only for gas in the control group. The percent reduction in thresholds for gas and pain after lipids was greater in the IBS and IBS-D groups but not in the IBS-C group compared with controls. IBS patients had an increased area of referred discomfort and pain after lipids compared with before infusion whereas the referral area remained unchanged in controls. No group differences in colonic tone or compliance were observed. In both groups higher levels of cholecystokinin, pancreatic polypeptide, peptide YY, vasoactive intestinal polypeptide, and neuropeptide Y were seen after lipids. Motilin levels were higher in patients and differences in the subgroups were observed. Levels of corticotrophin releasing factor were lower in the constipated group than in the diarrhoea group. CONCLUSIONS Postprandial symptoms in IBS patients may be explained in part by a nutrient dependent exaggerated sensory component of the gastrocolonic response.